O1009: Elevated Transplant Hazard in Pediatric Restrictive Cardiomyopathy: A TriNetX US Collaborative Network Study

Background: Pediatric cardiomyopathies present with diverse phenotypes and prognoses, with restrictive cardiomyopathy (RCM) often regarded as having the most aggressive clinical course. The decision to refer for heart transplantation is heavily influenced by disease subtype, but quantitative, risk-adjusted comparisons across phenotypes remain limited. This study applies a Cox proportional hazards framework to evaluate whether RCM independently predicts increased hazard of heart transplant compared to hypertrophic cardiomyopathy (HCM), using real-world, multi-center EHR data from TriNetX.

Methods: This retrospective cohort study utilized data from the TriNetX US Collaborative Network, comprising 68 healthcare organizations across the United States. Pediatric patients (aged ≤18 years) diagnosed with either restrictive cardiomyopathy (RCM) or hypertrophic cardiomyopathy (HCM), were identified using ICD-10 codes. RCM diagnoses were defined by the presence of restrictive cardiomyopathy codes and exclusion of secondary infiltrative or inflammatory conditions. The HCM group included both obstructive and non-obstructive subtypes under the same exclusion criteria.
The primary outcome was time to first heart transplant following the index diagnosis. A Cox proportional hazards model was constructed to evaluate the association between cardiomyopathy subtype and transplant risk, adjusting for relevant covariates such as age at diagnosis, sex, presence of heart failure (including subtypes), and exposure to cardioprotective medications. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported, and statistical significance was defined as p < 0.05. Patients with prior transplant were excluded from the analysis.

Results: Among 2,298 RCM and 5,002 HCM patients, those with RCM were older at diagnosis (mean age 13 vs. 10 years) and slightly less frequently male (53.6% vs. 58.7%). The model revealed a significantly elevated risk of heart transplant in RCM compared to HCM (HR 4.38, 95% CI 2.94–6.51, p < 0.001), indicating over a fourfold increase in transplant hazard [Figure 1]. Younger age at diagnosis was independently associated with increased transplant risk (HR 1.04, 95% CI 1.01–1.06, p = 0.003). Presence of heart failure (HR 2.44, 95% CI 1.72–3.46, p < 0.001) also significantly elevated transplant risk. Other heart failure subtypes, such as combined systolic and diastolic failure (HR 2.95, 95% CI 1.59–5.49), showed a similar trend. Use of ACE inhibitors (HR 2.21) and calcium channel blockers (HR 2.92), while not all statistically significant, may reflect treatment severity rather than causal relationships. The full model with hazard ratios and confidence intervals is illustrated in [Figure 2].

Conclusion: In this multivariable survival analysis, RCM was strongly and independently associated with a significantly elevated hazard of heart transplant in pediatric patients compared to HCM. The fourfold increase in hazard persisted after adjusting for clinical covariates including age, heart failure, and medication exposure. These findings support the aggressive nature of RCM and highlight the importance of early risk stratification and timely referral for transplant evaluation in this high-risk population.